(a) Field of the Invention
This invention relates to 2-(pyridinyl or hydroxyphenyl)8-substituted-pyrido[2,3-d]pyrimidin-5(8H)-ones, their preparation and their use as cardiotonics.
(b) Description of the Prior Art
Lesher and Singh [U.S. Pat. No. 3,992,380, issued Nov. 16, 1976] show as antibacterial agents, 5,8-dihydro-8-(lower-alkyl)-5-oxo-2-Q-4-R.sub.2 -6-Z-pyrido[2,3-d]pyrimidines where Z is carboxy or lower-carbalkoxy, R.sub.2 is hydrogen or lower-alkyl and Q is 4(or 3)-pyridinyl or 4(or 3)-pyridinyl having one or two lower-alkyl substituents. Said antibacterial agents are prepared by heating di-(lower-alkyl) N-(2-Q-6-R.sub.2 -4-pyrimidinyl)aminomethylenemalonate to produce 5,8-dihydro-5-oxo-2-Q-4-R.sub.2 -6-(lowercarbalkoxy)-pyrido[2,3-d]pyrimidine where Q and R.sub.2 are as defined above, reacting the latter with a lower-alkylating agent to produce the corresponding 8-(lower-alkyl) compound and hydrolyzing this compound to produce the 6-carboxy derivative.
Lesher and Singh [U.S. Pat. No. 4,018,770, issued Apr. 19, 1977] disclose and claim, inter alia, cyclic alkylidenyl N-[2-(pyridinyl)-4-pyrimidinyl]aminomethylenemalonate, e.g., isopropylidenyl N-[2-(4-pyridinyl)-4-pyrimidinyl]aminomethylenemalonate, alternatively named 2,2-dimethyl-5-&lt;{[2-(4-pyridinyl)-4-pyrimidinyl]amino}methyl&gt;1,3-dioxane-2 ,4-dione, which are used herein as intermediates.
Osselaere et al. [U.S. Pat. No. 3,873,545, issued Mar. 25, 1975], disclose, inter alia, 2-(3-pyridinyl or 4-pyridinyl)-3,4-dihydropyrido[2,3-d]pyrimidin-4-one as having spasmolytic and diuretic activities.
Matsumoto et al [Japanese Kokai 78 18,600, published Feb. 20, 1978; C.A. 89, 24,351d (1978)] show 8-ethyl-2-(1-piperazinyl)pyrido[2,3-d]pyrimidin-5-one hydrochloride as having analgesic activity in mice and antiinflammatory activity in rats.
Lesher [U.S. Pat. No. 3,642,797, issued Feb. 15, 1972] shows the preparation of a 4H-pyrido[1,2-a]pyrimidin-4-one by heating a cyclic alkylidenyl 2-pyridinylaminomethylenemalonate and also the preparation of a 4-hydroxyquinoline by heating a cyclic alkylidenyl anilinomethylenemalonate as well as the preparation of a 4-hydroxyquinoline by heating an aniline with a mixture of a trialkyl orthoformate and a cyclic alkylidenyl malonate.